Assessment of data quality in a multi-centre cross-sectional study of participation and quality of life of children with cerebral palsy

Background: SPARCLE is a cross-sectional survey in nine European regions, examining the relationship of the environment of children with cerebral palsy to their participation and quality of life. The objective of this report is to assess data quality, in particular heterogeneity between regions, family and item non-response and potential for bias. Methods: 1,174 children aged 8–12 years were selected from eight population-based registers of children with cerebral palsy; one further centre recruited 75 children from multiple sources. Families were visited by trained researchers who administered psychometric questionnaires. Logistic regression was used to assess factors related to family non-response and self-completion of questionnaires by children. Results: 431/1,174 (37%) families identified from registers did not respond: 146 (12%) were not traced; of the 1,028 traced families, 250 (24%) declined to participate and 35 (3%) were not approached. Families whose disabled children could walk unaided were more likely to decline to participate. 818 children entered the study of which 500 (61%) self-reported their quality of life; children with low IQ, seizures or inability to walk were less likely to self-report. There was substantial heterogeneity between regions in response rates and socio-demographic characteristics of families but not in age or gender of children. Item non-response was 2% for children and ranged from 0.4% to 5% for questionnaires completed by parents. Conclusion: While the proportion of untraced families was higher than in similar surveys, the refusal rate was comparable. To reduce bias, all analyses should allow for region, walking ability, age and socio-demographic characteristics. The 75 children in the region without a population based register are unlikely to introduce bias

Applying an Agility/Discipline Assessment for a Small Software Organisation

The adoption of agile software development methodologies may appear to be a rather straightforward process yielding instantly improved software in less time and increasingly satisfied customers. This paper will show that such a notion is a misunderstanding and can be harmful to small software development organisations. A more reasonable approach involves a careful risk assessment and framework for introducing agile practices to address specific risks. A case study with a small software development organisation is provided to show the assessment in practice and the resulting risk mitigation strategies for process improvement.

Knowledge-based risk assessment under uncertainty in engineering projects

In this paper we describe how an evidential-reasoner can be used as a component of risk assessment of engineering projects using a direct way of reasoning. Guan & Bell (1991) introduced this method by using the mass functions to express rule strengths. Mass functions are also used to express data strengths. The data and rule strengths are combined to get a mass distribution for each rule; i.e., the first half of our reasoning process. Then we combine the prior mass and the evidence from the different rules; i.e., the second half of the reasoning process. Finally, belief intervals are calculated to help in identifying the risks. We apply our evidential-reasoner on an engineering project and the results demonstrate the feasibility and applicability of this system in this environment.

Risk assessment of E-Commerce projects using evidential reasoning

The purpose of this study is to develop a decision making system to evaluate the risks in E-Commerce (EC) projects. Competitive software businesses have the critical task of assessing the risk in the software system development life cycle. This can be conducted on the basis of conventional probabilities, but limited appropriate information is available and so a complete set of probabilities is not available. In such problems, where the analysis is highly subjective and related to vague, incomplete, uncertain or inexact information, the Dempster-Shafer (DS) theory of evidence offers a potential advantage. We use a direct way of reasoning in a single step (i.e., extended DS theory) to develop a decision making system to evaluate the risk in EC projects. This consists of five stages 1) establishing knowledge base and setting rule strengths, 2) collecting evidence and data, 3) determining evidence and rule strength to a mass distribution for each rule; i.e., the first half of a single step reasoning process, 4) combining prior mass and different rules; i.e., the second half of the single step reasoning process, 5) finally, evaluating the belief interval for the best support decision of EC project. We test the system by using potential risk factors associated with EC development and the results indicate that the system is promising way of assisting an EC project manager in identifying potential risk factors and the corresponding project risks.

Further assessment of the complement component 2 and factor B region associated with age-related macular degeneration

PURPOSE. Polymorphic variation in genes involved in regulation of the complement system has been implicated as a major cause of genetic risk, in addition to the LOC387715/HTRA1 locus and other environmental influences. Previous studies have identified polymorphisms in the complement component 2 (CC2) and factor B (CFB) genes, as potential functional variants associated with AMD, in particular CFB R32Q and CC2 rs547154, both of which share strong linkage disequilibrium (LD). METHODS. Data derived from the HapMap Project were used to select 18 haplotype-tagging SNPs across the extended CC2/ CFB region for genotyping, to measure the strength of LD in 318 patients with neovascular AMD and 243 age-matched control subjects to identify additional potential functional variants in addition to those originally reported. RESULTS. Strong LD was measured across this region as far as the superkiller viralicidic activity 2-like gene (SKIV2L). Nine SNPs were identified to be significantly associated with the genetic effect observed at this locus. Of these, a nonsynonymous coding variant SKIV2L R151Q (rs438999; OR, 0.48; 95% confidence interval [CI], 0.31- 0.74; P < 0.001), was in strong LD with CFB R32Q, rs641153 (r2 = 0.95) and may exert a functional effect. When assessed within a logistic regression model measuring the effects of genetic variation at the CFH and LOC387715/HTRA1 loci and smoking, the effect remained significant (OR, 0.38; 95% CI, 0.22- 0.65; P < 0.001). Additional variation identified within this region may also confer a weaker but independent effect and implicate additional genes within the pathogenesis of AMD. CONCLUSIONS. Because of the high level of LD within the extended CC2/CFB region, variation within SKIV2L may exert a functional effect in AMD. Copyright © Association for Research in Vision and Ophthalmology.

Clinical and immunohistochemical assessment of vulval intraepithelial neoplasia following photodynamic therapy using a novel bioadhesive patch-type system loaded with 5-aminolevulinic acid

Background: The work in this study appraised photodynamic treatment (PDT) as a treatment method for vulval intraepithelial neoplasia (VIN) using a novel bioadhesive patch to deliver aminolevulinic acid. An analysis of changes in expression of apoptotic and cell cycle proteins (p53, p21, Mdm2, Blc-2, Bax, Ki-67) in response to PDT was evaluated. Methods: PDT was performed using non-laser light, either as a one or two-cycle treatment, with clinical and pathological assessment following after 6 weeks. Twenty-three patients with 25 VIN lesions underwent 49 cycles of PDT Patches were designed to conform to uneven vulval skin and contained 38 mg cm(-2) aminolevulinic acid. Assessment was carried out at 6 weeks post-treatment. Patient-based treatment assessment, along with clinical and pathological changes, were monitored. Immunohistochemical staining was used to elucidate a possible biomolecular basis for induced cellular changes. Results: Most patients (52%) reported a symptomatic response, with normal pathology restored in 38% of lesions. The patch was easy to apply and remove, causing minimal discomfort. Fluorescence inspection confirmed protoporphyrin accumulation. Pain during implementation of PDT was problematic, necessitating some form of local analgesia. Changes in expression of cell cycle and apoptotic-related proteins suggested involvement of apoptotic pathways. Down regulation of p21 and inverse changes in Bcl-2 and Bax were key findings. Conclusion: Treatment of VIN lesions using a novel bioadhesive patch induced changes in cell cycle and apoptotic proteins in response to PDT with possible utilisation of apoptotic pathways. The efficacy of PDT in treating VIN could be improved by a better understanding of these apoptotic mechanisms, the influence of factors, such as HPV status, and of the need for effective pain management.

An assessment of the earth pressure coefficient in overconsolidated clays

The determination of the earth pressure coefficient K 0 in a natural clay deposit is a problem of considerable significance in geotechnical engineering. While the methods for evaluation of K 0 are reliable for normally consolidated soils, significant difficulties still exist in evaluating K 0 in overconsolidated clays, given that it is influenced by the stress history of the material, together with the age, structure, mineralogical composition and depositional environment. Indeed, some of these factors are responsible for the soil becoming anisotropic. The existing framework for prediction of K 0 in overconsolidated soils does not account for any influences caused by anisotropy. The work reported in this paper evaluates the validity of a revised relationship between K 0oc and OCR (overconsolidation ratio) using data obtained from laboratory investigations. The tests were performed on reconstituted and undisturbed samples of Belfast Upper Boulder Clay, London Clay and Gault Clay. Tests were also performed on reconstituted samples of kaolin. The values of K 0oc were determined using various approaches, including on-sample measurements. The results have confirmed that reliable predictions of K 0oc can be made using the proposed relationship.

An audit of assessment and reporting by Approved Social Workers (ASWs)

This paper examines the routine practice of Approved Social Workers (ASWs) in adult mental health services in Northern Ireland. It begins with a review of existing literature on the ASW role before describing how a retrospective audit, using a mixed methods approach, was used to collect data on eighty-four assessments carried out to determine whether compulsory admission to hospital was needed. Respondents were also asked to consider how such assessments might be affected by proposed changes to the law in this field. The key findings highlighted a number of areas of practice that may be improved. There were inconsistencies in how the assessments were recorded and an uneven distribution of workloads across ASWs. Some problems were identified with interagency working and, in a quarter of the assessments, the ASW reported having felt afraid or at risk. The authors make a number of recommendations, which include: the use of a standard reporting procedure; that organisations should consider how to deliver a more even distribution of ASW workload; that protocols should be developed that ensure that ASWs are not left alone in potentially risky situations; and that joint assessments with General Practitioners should be required, rather than just recommended.

Multi-Study Assessment of Vaginal Cytokines and Microflora in the Safety Evaluation of Intravaginal Rings in Pig-Tailed Macaques

BACKGROUND: HIV microbicide trials have emphasized the need to evaluate the safety of topical microbicides and delivery platforms in an animal model prior to conducting clinical efficacy trials. An ideal delivery device should provide sustainable and sufficient concentrations of effective products to prevent HIV transmission while not increasing transmission risk by either local mucosal inflammation and/or disruption of the normal vaginal microflora.

METHODS: Safety analyses of macaque-sized elastomeric silicone and polyurethane intravaginal rings (IVRs) loaded with candidate antiretroviral (ARV) drugs were tested in four studies ranging in duration from 49 to 73 days with retention of the IVR being 28 days in each study. Macaques were assigned to 3 groups; blank IVR, ARV-loaded IVR, and naïve. In sequential studies, the same macaques were used but rotated into different groups. Mucosal and systemic levels of cytokines were measured from vaginal fluids and plasma, respectively, using multiplex technology. Changes in vaginal microflora were also monitored. Statistical analysis (Mann-Whitney test) was used to compare data between two groups of unpaired samples (with and without IVR, and IVR with and without ARV) for the groups collectively, and also for individual macaques.

RESULTS: There were few statistically significant differences in mucosal and systemic cytokine levels measured longitudinally when the ring was present or absent, with or without ARVs. Of the 8 proinflammatory cytokines assayed a significant increase (p = 0.015) was only observed for IL8 in plasma with the blank and ARV loaded IVR (median of 9.2 vs. 5.7 pg/ml in the absence of IVR). There were no significant differences in the prevalence of H2O2-producing lactobacilli or viridans streptococci, or other microorganisms indicative of healthy vaginal microflora. However, there was an increase in the number of anaerobic gram negative rods in the presence of the IVR (p= < 0.0001).

CONCLUSIONS: IVRs with or without ARVs neither significantly induce the majority of potentially harmful proinflammatory cytokines locally or systemically, nor alter the lactobacillus or G. vaginalis levels. The increase in anaerobic gram negative rods alone suggests minimal disruption of normal vaginal microflora. The use of IVRs as a long-term sustained delivery device for ARVs is promising and preclinical studies to demonstrate the prevention of transmission in the HIV/SHIV nonhuman primate model should continue.

Response shift in the assessment of quality of life among people attending cardiac rehabilitation

Objectives: To examine whether any response shift in quality of life assessment over the course of a cardiac rehabilitation programme could be explained by changes in individuals’ internal standards (recalibration), values (reprioritization) and/or conceptualization of quality of life and the extent to which any response shift could be explained by health locus of control, optimism and coping strategy. Design: Longitudinal survey design. Methods: The SEIQoL-DW was administered at the beginning and end of a cardiac rehabilitation programme. At the end of the programme, the SEIQoL-DW then-test was also administered to measure response shift. A total of 57 participants completed these measures and other measures to assess health locus of control, optimism and coping. Results: Response shift effects were observed in this population mainly due to recalibration. When response shift was incorporated into the analysis of QoL a larger treatment effect was observed. Active coping as a mechanism in the response shift model was found to have a significant positive correlation with response shift. Conclusion: This study showed that response shift occurs during cardiac rehabilitation. The occurrence of response shift in QoL ratings over time for this population could have implications for the estimation of the effectiveness of the intervention.

Assessment of fighting ability in animal contests

Selection should favour accurate information gathering regarding the likely costs and benefits of continued conflict. Here we consider how variation in the abilities of contestants to assess resource-holding potential (RHP) influences fights. This has been examined in various game theory models. However, discriminating between assessment strategies has proven difficult and has resulted in confusion. To add clarity, we group existing models into three main types that differ in the information about RHP that contestants are presumed to gather: (1) pure self-assessment, (2) cumulative assessment and (3) mutual assessment. Within this framework we outline methods advocated to discriminate successfully between the three main assessment models. We discuss support for each model, before highlighting a number of conflicting and inconclusive studies, leading us to consider alternative approaches to investigate assessment. Furthermore, we examine support for newly emerging concepts such as 'varying degrees of assessment', 'switching assessment' strategies and the possibility of contestants adopting different assessment strategies within a fight involving distinctive roles. We suggest future studies will benefit by judicious use of a battery of techniques to determine how animals settle contests. Finally, we highlight difficulties with current game theory models, and raise concerns regarding the use of certain behavioural criteria to accept or reject a model, particularly since this may conflict with evidence for a given assessment strategy. Furthermore, the failure of existing models to account for newly emerging concepts points to limitations of their use and leads us to challenge game theoreticians to develop upon them. (C) 2009 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Remote Detection and Identification of Organic Remains: An Assessment of Archaeological Potential

This paper reviews the various methods of using natural or induced light spectra as analytical tools in forensic archaeology. Chemical identi?cation can be made at long range and wide scale (tens of metres) down to short range and very small scale (nanometres). The identi?cation of organic gases and materials has used either chemical capture and chromatography, induced (laser or ultraviolet) light sources or laser Raman microscope spectroscopy. The remote gas detection method relies on the identi?cation of atmospheric gases by their characteristic light spectra. Modern spectroscopes can detect gases down to a few parts per million of an atmosphere. When the light source (wavelength) and direction is controlled, so laser-induced spectroscopy may be used to monitor the emission of gases such methane from buried organic remains. In order to identify the location of buried organic remains, a grid of sample points must be established using a base line or global
positioning system. When matched to base line or ground-positioning systems, such data can be manipulated by geographical information system packages. This would enable pinpointing of anomalies for excavation or avoidance. Microscope-based laser Raman spectroscopy can be used to directly analyse captured gases, swabs and surfaces without the problems of long-path detection. Copyright ? 2002 John Wiley & Sons, Ltd.

Tumor Risks and Genotype-Phenotype-Proteotype Analysis in 358 Patients With Germline Mutations in SDHB and SDHD

Succinate dehydrogenase B (SDHB) and D (SDHD) subunit gene mutations predispose to adrenal and extraadrenal pheochromocytomas, head and neck paragangliomas (HNPGL), and other tumor types. We report tumor risks in 358 patients with SDHB (n = 295) and SDHD (n = 63) mutations. Risks of HNPGL and pheochromocytoma in SDHB mutation carriers were 29% and 52%, respectively, at age 60 years and 71% and 29%, respectively, in SDHD mutation carriers. Risks of malignant pheochromocytoma and renal tumors (14% at age 70 years) were higher in SDHB mutation carriers; 55 different mutations (including a novel recurrent exon 1 deletion) were identified. No clear genotype-phenotype correlations were detected for SDHB mutations. However, SDHD mutations predicted to result in loss of expression or a truncated or unstable protein were associated with a significantly increased risk of pheochromocytoma compared to missense mutations that were not predicted to impair protein stability (most such cases had the common p.Pro81Leu mutation). Analysis of the largest cohort of SDHB/D mutation carriers has enhanced estimates of penetrance and tumor risk and supports in silicon protein structure prediction analysis for functional assessment of mutations. The differing effect of the SDHD p.Pro81Leu on HNPGL and pheochromocytoma, risks suggests differing mechanisms of tumorigenesis in SDH-associated HNPGL and pheochromocytoma. Hum Mutat 31:41-51, 2010. (C) 2009 Wiley-Liss, Inc.

High-Frequency Ultrasound Assessment of the Murine Heart From Embryo Through to Juvenile

Aim: The aim of this study is to assess the murine heart of normal embryos, neonates, and juveniles using high-frequency ultrasound. Methods: Diastolic function was measured with E/A ratio (E wave velocity/A wave velocity) and isovolumetric relaxation time (IRT), systolic function with isovolumetric contraction time (ICT), percentage fractional shortening (FS%), percentage ejection fraction (EF%). Global cardiac performance was quantified using myocardial performance index (MPI). Results: Isovolumetric relaxation time remained stable from E10.5 to 3 weeks. Systolic function (ICT) improved with gestation and remained stable from E18.5 onward. Myocardial performance index showed improvement in embryonic lift (0.82-0.63) and then stabilized from 1 to 3 week (0.60-0.58). Percentage ejection fraction remained high during gestation (77%-69%) and then decreased from the neonate to juvenile (68%-51%). Conclusion: The ultrasound biomicroscope allows for noninvasive in-depth assessment of cardiac function of embryos and pups. Detailed physiological and functional cardiac function readouts can be obtained, which is invaluable for comparison to mouse models of disease.

The use of process simulation methods in support of organisational learning in availability contracting

Traditional business models in the aerospace industry are based on a conventional supplier to customer relationship based on the design, manufacture and subsequent delivery of the physical product. Service provision, from the manufacturer's perspective, is typically limited to the supply of procedural documentation and the provision of spare parts to the end user as the product passes through the latter stages of its intended lifecycle. Challenging economic and political conditions have resulted in end users re-structuring their core business activities, particularly in the defence sector. This has resulted in the need for original equipment manufacturers (OEMs) to integrate and manage support service activities in partnership with the customer to deliver platform availability. This improves the probability of commercial sustainability for the OEM through shared operational risks while reducing the cost of platform ownership for the customer. The need for OEMs to evolve their design, manufacture and supply strategies by focusing on customer requirements has revealed a need for reconstruction of traditional internal behaviours and design methodologies. Application of organisational learning is now a well recognised principle for innovative companies to achieve long term growth and sustained technical development, and hence, greater market command. It focuses on the process by which the organisation's knowledge and value base changes, leading to improved problem solving ability and capacity for action. From the perspective of availability contracting, knowledge and the processes by which it is generated, used and retained, become primary assets within the learning organisation. This paper will introduce the application of digital methods to asset management by demonstrating how the process of learning can benefit from a digital approach, how product and process design can be integrated within a virtual framework and finally how the approach can be applied in a service context.